DESCRIPTION: (Applicant's Abstract) The broad objectives of this project are to further define attention impairment and associated brain function abnormalities in substance abusers (SA) with co-morbid posttraumatic stress disorder (PTSD). The relative contributions of substance abuse and PTSD would be assessed. Control state PET scans will clarify the interpretation of brain changes seen during attention. Since PTSD symptomatology is present in 25-45% of SA who seek treatment, attention and cognitive impairment in SA-PTSD represents both a vulnerability and treatment relapse factor in a large segment of the substance abusing population. Females constitute nearly 40% of SA, and appear to have increased rates of co-morbid SA-PTSD compared to males. The specific objectives of this project are to examine auditory continuous performance task (ACPT) impairment and related brain dysfunction in cocaine abusers with and without co-morbid PTSD who are at least 4 weeks drug free. Ongoing regional cerebral blood flow (rCBF) studies of attention using '50-butanol and positron emission tomography (PET) will be expanded to include women to test the generality of findings in males. SA-PTSD, SA-Only, PTSD-Only, and normal groups will be compared. Six serial PET scans using 0-15 butanol will assess rCBF in frontal, parietal, and anterior cingulate cortex attention substrates during rest, the ACPT, and an auditory tone/no response control state. Image analysis will incorporate region of interest and statistical parametric mapping techniques. Additional clinical and neuropsychological testing will assess symptomatology, pre-morbid characteristics, and cognitive impairment. Hypotheses to be tested include: 1) SA-PTSD patients will show impaired attention compared to SA-Only, PTSD-Only, and normal controls; 2) SA-PTSD patients will show reduced parietal rCBF compared to normal controls and PTSD-Only, with SA-Only intermediate; 3) Compared to normals, SA-PTSD and SA-Only will have decreased rCBF at anterior cingulate during the ACPT; 4) SA-PTSD and SA-Only patients will have normal rCBF levels and activation of the right prefrontal cortex; 5) Females with SA-PTSD will have attention impairment and parietal abnormalities like those seen in males; 6) Attention performance impairment will be correlated with brain attention substrate dysfunction. The proposed project seeks to identify a brain pathophysiology for behavioral impairment related to vulnerability for substance abuse and treatment relapse.